Et-1 and Et-3 actions mediated by cloned ETA endothelin receptors exhibit different sensitivities to BQ-123

Et-1 and Et-3 activate phospholipase C in fibroblasts expressing cloned ETA receptors of bovine, rat and human origins. BQ-123 competitively antagonizes both responses but Et-3 actions are 10 times more sensitive to BQ-123 than Et-l actions. It is suggested that differential sensitivity to BQ-123 is an intrinsic property of Et-l and Et-3 activated ETA receptors and that there is no need to postulate the existence of new ETA receptor isoforms to account for singular actions of BQ-123. (C) 1996 Academic Press, Inc.